ArticleInternational journal of cancer2014
Paracrine activation of hepatic stellate cells in platelet-derived growth factor C transgenic mice: evidence for stromal induction of hepatocellular carcinoma.
Article in International journal of cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 75 citations in OpenAlex.
- An Inhibitory Aptamer Against PDGF-C Overcomes Anti-VEGF Refractoriness and Reduces Choroidal Neovascularization and Fibrosis.Investigative ophthalmology & visual science · 2026Article
- Single-cell insights into tumor microenvironment heterogeneity and plasticity: transforming precision therapy in gastrointestinal cancers.Journal of experimental & clinical cancer research : CR · 2025Review
- Present and Future Perspectives in the Treatment of Liver Fibrosis.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Roles of PDGF/PDGFR signaling in various organs.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025Review
- An integrated investigation of sulfotransferases (SULTs) in hepatocellular carcinoma and identification of the role of SULT2A1 on stemness.Apoptosis : an international journal on programmed cell death · 2024Article
- Identification of ligand and receptor interactions in CKD and MASH through the integration of single cell and spatial transcriptomics.PloS one · 2024Article
- Friend or foe? The elusive role of hepatic stellate cells in liver cancer.Nature reviews. Gastroenterology & hepatology · 2023Review
- Mechanism of paracrine communications between hepatic progenitor cells and endothelial cells.Cellular signalling · 2022Article
- Advances of cancer-associated fibroblasts in liver cancer.Biomarker research · 2022Review
- Isolation and characterization mesenchymal stem cells from red panda (Conservation physiology · 2022Article
- Hepatic stellate and endothelial cells maintain hematopoietic stem cells in the developing liver.The Journal of experimental medicine · 2021Article
- The Role of Cancer-Associated Fibroblasts in Hepatocellular Carcinoma and the Value of Traditional Chinese Medicine Treatment.Frontiers in oncology · 2021Review
- Analysis of key genes and related transcription factors in liver fibrosis based on bioinformatic technology.International journal of clinical and experimental pathology · 2021Article
- Identifying cancer-associated fibroblasts as emerging targets for hepatocellular carcinoma.Cell & bioscience · 2020Review
- Metabolic inflammation as an instigator of fibrosis during non-alcoholic fatty liver disease.World journal of gastroenterology · 2020Review
- Norepinephrine-stimulated HSCs secrete sFRP1 to promote HCC progression following chronic stress via augmentation of a Wnt16B/β-catenin positive feedback loop.Journal of experimental & clinical cancer research : CR · 2020Article
- Hepatic Stellate Cells and Hepatocarcinogenesis.Frontiers in cell and developmental biology · 2020Review
- Review
- Lesion Dynamics Under Varying Paracrine PDGF Signaling in Brain Tissue.Bulletin of mathematical biology · 2019Article
- Recent Insight into the Role of Fibrosis in Nonalcoholic Steatohepatitis-Related Hepatocellular Carcinoma.International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 2 countries.
Funding
Abstract
Cirrhosis is the primary risk factor for the development of hepatocellular carcinoma (HCC), yet the mechanisms by which cirrhosis predisposes to carcinogenesis are poorly understood. Using a mouse model that recapitulates many aspects of the pathophysiology of human liver disease, we explored the mechanisms by which changes in the liver microenvironment induce dysplasia and HCC. Hepatic expression of platelet-derived growth factor C (PDGF-C) induces progressive fibrosis, chronic inflammation, neoangiogenesis and sinusoidal congestion, as well as global changes in gene expression. Using reporter mice, immunofluorescence, immunohistochemistry and liver cell isolation, we demonstrate that receptors for PDGF-CC are localized on hepatic stellate cells (HSCs), which proliferate, and transform into myofibroblast-like cells that deposit extracellular matrix and lead to production of growth factors and cytokines. We demonstrate induction of cytokine genes at 2 months, and stromal cell-derived hepatocyte growth factors that coincide with the onset of dysplasia at 4 months. Our results support a paracrine signaling model wherein hepatocyte-derived PDGF-C stimulates widespread HSC activation throughout the liver leading to chronic inflammation, liver injury and architectural changes. These complex changes to the liver microenvironment precede the development of HCC. Further, increased PDGF-CC levels were observed in livers of patients with nonalcoholic fatty steatohepatitis and correlate with the stage of disease, suggesting a role for this growth factor in chronic liver disease in humans. PDGF-C transgenic mice provide a unique model for the in vivo study of tumor-stromal interactions in the liver.
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Registered trials
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